Neuropeptide Y (hereinafter abbreviated as NPY) is a peptide consisting of 36 amino acids, which was isolated from porcine brain for the first time by Tatemoto et al. in 1982 [Nature, vol.296, p.659 (1982)]. NPY is broadly distributed in central and peripheral nervous systems and has various in vivo functions as one of the peptides most abundantly present in the nervous systems. That is, in the central nervous system, NPY acts as an aperitive and significantly promotes a fat accumulation associated with the lowering of a basal metabolism via secretion of various hormones and actions of the nervous systems. It is known that a continuous intracerebroventricular administration of NPY induces obesity and insulin resistance based on the above actions. And, it is known that in rodents showing hereditary or dietary obesity, NPY concentration in the brain is increased. Further, the increase in expression of the NPY receptor is reported. NPY is also associated with the control of mood and functions of the central autonomic nervous system. In addition, in the peripheral nervous system, NPY is present together with norepinephrine in the sympathetic nerve terminal and associated with the tension of the sympathetic nervous system [International Journal of Obesity, vol.19, p.517 (1995); Endocrinology, vol.133, p.1753 (1993); Neuropeptide Y and drug development, p.15 (1997); Brain Research, vol.744, p.1 (1997); The biology of neuropeptide Y, p.315 (1993)].
The function of NPY is expressed when it is bound to an NPY receptor present in the central or peripheral nervous system. Therefore, the expression of the function of NPY can be prevented if the binding of NPY to the NPY receptor is inhibited. Consequently, it is expected that compounds capable of antagonizing the binding of NPY to the NPY receptor are useful in the prevention or treatment of various diseases associated with NPY, for example, diseases of circulatory organs such as hypertension, nephropathy, cardiopathy and angiospasm; diseases of central nervous system such as bulimia, depression, epilepsy and dementia; metabolic diseases such as obesity, diabetes and dysendocrisiasis, or glaucoma [Trends in Pharmacological Sciences, vol.15, p.153 (1994)].
Compounds structurally similar to the compounds related to the present invention are disclosed in Eur. J. Med. Chem., vol.23, No.2, p.111 (1988); J. Organic Chemistry, vol.31, No.5, p.1639 (1966); JP-49125364A; U.S. Pat. Nos. 3,414,587, 3,454,577, 3,536,757 and 3,539,590; and etc. Especially, J. Organic Chemistry, vol.31, No.5, p.1639 (1966) clearly discloses the compound related to the present invention.
However, an antagonistic action to NPY of the compound in question is not described at all therein.